Identification of cellular targets involved in cardiac failure caused by PKI in oncology: an approach combining pharmacovigilance and pharmacodynamics

Campaigno, Emilie Patras de; Bondon‐Guitton, Emmanuelle; Guy, Laurent; Montastruc, François; Montastruc, Jean‐Louis; Lapeyre‐Mestre, Maryse; Despas, Fabien

doi:10.1111/bcp.13238

Cited by 30 publications

(28 citation statements)

References 30 publications

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“…The direct combination of pharmacovigilance with pharmacodynamic data has been proposed to study receptor mechanisms of adverse events in safety reports databases. This approach has been applied in VigiBase to study drug-induced arrhythmias [29], antipsychotic-induced diabetes [4], antipsychotic-induced movement disorders [8] and cardiac failure induced by protein kinase inhibitors [9]. Herein, we used a similar approach Safety signal of antidepressants and type 2 diabetes in FAERS, which can also be used to study receptor mechanisms of adverse events [30].…”

Section: Figurementioning

confidence: 99%

“…In the present study, a combined pharmacovigilancepharmacodynamic approach was used [4,8,9]: (i) to detect a potential safety signal of antidepressants-induced type 2 diabetes (T2D) using disproportionality analysis in the FDA adverse events reporting system (FAERS), and (ii) to investigate the association between the risk for reporting diabetes and the occupancy on neurotransmitter receptors and transporters.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Detecting a potential safety signal of antidepressants and type 2 diabetes: a pharmacovigilance‐pharmacodynamic study

Siafis

Papazisis

2018

Brit J Clinical Pharma

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Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Detecting a potential safety signal of antidepressants and type 2 diabetes: a pharmacovigilance‐pharmacodynamic study

Siafis

Papazisis

2018

Brit J Clinical Pharma

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“…In the literature, some data on cardiac disorders associated with AZA such as atrial fibrillation and pleuro‐pericardial effusion were retrieved (see Table ), but with a frequency below 5%. Furthermore, data about the occurrence of CF in patients treated with AZA are scarce.…”

Section: Discussionmentioning

confidence: 99%

“…The pathophysiological mechanisms for the occurrence of CF in patients treated with AZA remain elusive. Some authors suggested that this toxicity could be a class effect of hypomethylating agents . Recently, Ambesh et al .…”

Section: Discussionmentioning

confidence: 99%

Cardiac failure in patients treated with azacitidine, a pyrimidine analogue: Case reports and disproportionality analyses in Vigibase

Perino

Mottal

Bohbot

et al. 2020

Brit J Clinical Pharma

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Aims: Azacitidine (AZA), a pyrimidine analogue, is validated for high-risk myelodysplastic syndrome or low-blast acute myeloid leukaemia in unfit patients for more intensive treatment. This study assessed the putative link between cardiac failure (CF) and AZA exposure.Methods: Cases of CF in patients treated with AZA were retrospectively collected and described from several centres of the Groupe Francophone des Myélodysplasies. A description analysis and a disproportionality analysis using Vigibase, the WHO Global Individual Case Safety Reports (ICSRs) database, were conducted on ICSRs by the Standardized MedDRA Queries (SMQ broad) cardiac failure and by preferred terms cardiac failure and cardiac failure acute. The reported odds ratio (ROR) and its 95% 2-sided confidence interval was computed by comparing the proportion of CF reports with the suspected drug (AZA) and the proportion of reports of the same adverse drug reaction with all other suspected drugs in the database during the same period. Results:In the 4 case reports, all patients presented a cardiovascular history. In 1 patient, CF recurred after AZA re-challenge. The pharmacovigilance analysis in Vigibase retrieved 307 ICSRs of CF (SMQ) with AZA. Significant disproportionality signals associated with AZA were identified by using the SMQ cardiac failure (ROR 1.3) and the preferred terms cardiac failure (ROR 5.1) and cardiac failure acute (ROR 23.2). Conclusion:This study points to the potential role of AZA in the occurrence of CF. Cardiac evaluation before AZA initiation and regular monitoring of cardiac function during AZA treatment should be performed in patients with a history of cardiovascular disease. K E Y W O R D Santicancer drugs, drug safety, heart failure

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“…Side effects of afatinib include skin rash [6], xerosis [6], paronchia [6], stomatitis [6,41], diarrhea [6,41], heart failure [42], neutropenia [41], leukopenia [41], and anemia [41,43]. Afatinib is in part effective by inducing apoptosis [44][45][46][47][48][49][50][51][52][53][54][55][56][57], an effect involving oxidative stress [46].…”

Section: Introductionmentioning

confidence: 99%

Stimulation of Eryptosis by Afatinib

Bhuyan

Läng

2018

Cell Physiol Biochem

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Background/Aims: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor afatinib is primarily utilized for the treatment of non-small cell lung carcinoma. The drug is at least partially effective by triggering suicidal tumor cell death. Side effects of afatinib treatment include anemia. At least in theory, afatinib induced anemia could be secondary to stimulation of suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling potentially stimulating eryptosis include increase of cytosolic Ca 2+ activity ([Ca 2+ ] i ), induction of oxidative stress, and increase of ceramide abundance. The present study explored, whether afatinib induces eryptosis and, if so, whether its effect involves Ca 2+ entry, oxidative stress, and/or ceramide. Methods: Flow cytometry was employed to quantify phosphatidylserine exposure at the cell surface from annexin-V-binding, cell volume from forward scatter, [Ca 2+ ] i from Fluo3-fluorescence, reactive oxygen species (ROS) abundance from DCFDA dependent fluorescence, and ceramide abundance utilizing specific antibodies. Results: A 48 hours exposure of human erythrocytes to afatinib (≥ 4 µg/ml) significantly increased the percentage of annexin-V-binding cells and significantly decreased forward scatter. Afatinib significantly increased Fluo3-fluorescence, DCFDA fluorescence and ceramide abundance. The effect of afatinib on annexin-V-binding and forward scatter was significantly blunted by removal of extracellular Ca 2+ . Conclusions: Afatinib triggers phospholipid scrambling of the erythrocyte cell membrane, an effect at least in part due to Ca 2+ entry, oxidative stress, and ceramide.

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Identification of cellular targets involved in cardiac failure caused by PKI in oncology: an approach combining pharmacovigilance and pharmacodynamics

Abstract: We observed a higher disproportionality for CF with dasatinib, imatinib, bosutinib, sunitinib and nilotinib than with other PKIs. In addition, the study highlighted the role of ABL tyrosine kinases in CF caused by anticancer PKIs.

Cited by 30 publications

References 30 publications

Detecting a potential safety signal of antidepressants and type 2 diabetes: a pharmacovigilance‐pharmacodynamic study

Detecting a potential safety signal of antidepressants and type 2 diabetes: a pharmacovigilance‐pharmacodynamic study

Cardiac failure in patients treated with azacitidine, a pyrimidine analogue: Case reports and disproportionality analyses in Vigibase

Stimulation of Eryptosis by Afatinib

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